Abnormal rest and exercise left ventricular ejection fraction and increased lung uptake of thallium during exercise identify coronary artery disease patients at high risk for future cardiac events. To determine whether technetium-99m sestamibi lung/heart ratio during exercise and the extent of exercise-induced sestamibi perfusion defects also correlate with known indices of adverse prognosis, 12 patients with chronic coronary artery disease underwent both same-day rest-exercise sestamibi tomography and rest and exercise radionuclide angiography studies within a mean of 8 days. Prior to sestamibi exercise studies, Swan-Ganz catheters were placed in all patients. Pulmonary capillary wedge pressure measured at baseline ranged from 7 to 43 mm Hg (mean 19 mm Hg) and at peak exercise ranged from 7 to 47 mm Hg (mean 27mm Hg). Images were acquired within a mean of 25 minutes from the time of sestamibi injection during treadmill exercise. Quantitative sestamibi lung/heart ratios were calculated from the anterior projections and based on previously published data, lung/heart ratio more than0.42 was considered abnormal. Mean left ventricular ejection fraction at rest was 29% (range 10% to 50%) and decreased to 25% during exercise (range 6% to 44%). The number of exercise-induced sestamibi defects per patient (mean 2.33/patient) correlated significantly with their respective exercise pulmonary capillary wedge pressure measurements (r=0.59, pless than0.04). While pulmonary capillary wedge pressure was inversely correlated with left ventricular ejection fraction both at rest (r=-0.73, pless than0.01) and during exercise (r=-0.87, pless than0.01), there was no correlation between pulmonary capillary wedge pressure and sestamibi lung/heart ratio (r=0.42, p=NS). These data suggest that unlike increased lung/heart ratio of thallium, sestamibi lung/heart ratios during exercise may not be useful in identifying coronary artery disease patients at high risk for future cardiac events.